Ridgefield, CT, April 4, 2011 – Two new retrospective subanalyses of the RE-LY ® trial, involving Pradaxa ® (dabigatran etexilate mesylate) capsules, suggested that the reduction in stroke risk achieved with PRADAXA 150mg over warfarin 1 occurred irrespective of CHA 2DS 2-VASc risk score 2 and the type of non-valvular atrial fibrillation (NVAF) (permanent, persistent and paroxysmal). 3 The results were presented at the American College of Cardiology’s 60th Annual Scientific Session. 2,3
The first subanalysis assessed the impact of the novel CHA 2DS 2-VASc risk score, 2 which determines stroke risk based on age, sex and the presence of comorbidities, 4 on outcomes in the RE-LY trial. Patients were grouped into quartiles based on CHA 2DS 2-VASc score (0-2, 3, 4, 5-9) 2 and results showed that PRADAXA 150mg was associated with reductions in stroke risk compared to warfarin for all four quartiles (0-2, RR = 0.63; 3, RR = 0.61; 4, RR = 0.53; 5-9, RR = 0.77; interaction p-value = 0.60). 2 Results of the analysis showed there was a significant interaction between CHA 2DS 2-VASc score and rates of major bleeding, with lower rates for PRADAXA 150mg compared to warfarin for patients in the first three quartiles, but an increased rate of major bleeding for the quartile at greatest risk (0-2, RR = 0.75; 3, RR = 0.74; 4, RR = 0.83; 5-9, RR = 1.33; interaction p-value = 0.003). 2
"This analysis suggests that PRADAXA 150mg taken twice daily may reduce the risk of stroke compared to warfarin across the levels of NVAF-associated stroke risk, as determined by the CHA 2DS 2-VASc score," said Paul Reilly, PhD, clinical program director, Boehringer Ingelheim Pharmaceuticals, Inc. "These findings are important because the risk of stroke in patients with NVAF increases significantly with the presence of comorbidities, such as diabetes or hypertension."
PRADAXA was also evaluated in a second RE-LY subanalysis, which assessed efficacy and safety among the 18,107 patients for whom information was available about the type of NVAF 3 they had - permanent (long-standing), 5 paroxysmal (arrhythmia terminating spontaneously) 5 or persistent (lasting beyond seven days). 5 Findings showed that PRADAXA 150mg reduced the risk of stroke and systemic embolism compared to warfarin across all three subgroups (permanent, HR = 0.7; paroxysmal, HR = 0.61; persistent, HR = 0.64; interaction p-value = 0.88). 3,6 The analysis also showed the following rates of major bleeding: permanent: PRADAXA 150mg: 3.07%/yr, warfarin: 2.96%/yr; paroxysmal: PRADAXA 150mg: 3.74%/yr, warfarin: 3.91%/yr; persistent: PRADAXA 150mg: 3.14%/yr, warfarin: 3.88%/yr (interaction p-value = 0.34). 3,6
"Stroke risk is similar regardless of the type of non-valvular atrial fibrillation," said Greg Flaker, M.D., chair of cardiovascular research, University of Missouri. "These data showed PRADAXA 150mg twice daily was associated with lower rates of stroke than warfarin in patients with all three types of non-valvular atrial fibrillation."
PRADAXA was approved by the U.S. Food and Drug Administration in October 2010 to reduce the risk of stroke and systemic embolism in patients with NVAF. 1 PRADAXA 150mg is the only approved oral anticoagulant that has been shown to significantly reduce the risk of stroke compared to warfarin. 1 Effects of Pradaxa were more apparent in patients with lower levels of INR control. 1
Dabigatran was recently recommended in an update to AFib treatment guidelines.
Results from the CHA2DS2-VASc Subanalysis
In the subanalysis, patients were grouped into quartiles based on CHA 2DS 2-VASc score (0-2, n = 4,042; 3, n = 5,365; 4, n = 4,374; 5-9, n = 4,327). 2 The results of the subanalysis showed that PRADAXA 150mg was associated with reductions in stroke risk compared to warfarin for all four quartiles (0-2: PRADAXA 150 mg: 0.5%/yr, warfarin: 0.8%/yr; 3: PRADAXA 150mg: 0.8%/yr, warfarin: 1.4%/yr; 4: PRADAXA 150mg: 1.0%/yr, warfarin: 2.0%/yr; 5-9: PRADAXA 150mg: 2.1%/yr, warfarin: 2.8%/yr; interaction p-value = 0.60). 2
Results of the analysis showed there was a significant interaction between CHA 2DS 2-VASc score and rates of major bleeding, with lower rates for PRADAXA 150mg compared to warfarin for patients in the first three quartiles, but an increased rate of major bleeding for the quartile at greatest risk (0-2: PRADAXA 150mg: 1.8%/yr, warfarin: 2.4%/yr; 3: PRADAXA 150mg: 2.6%/yr, warfarin: 3.5%/yr; 4: PRADAXA 150mg: 3.2%/yr, warfarin: 3.9%/yr; 5-9: PRADAXA 150mg: 5.8%/yr, warfarin: 4.4%/yr; interaction p-value =0.003). 2
Results from the Different Types of NVAF Subanalysis
In the subanalysis, patients were classified by type of NVAF - 6,375 had permanent NVAF, 3 5,943 had paroxysmal NVAF 3 and 5,789 had persistent NVAF. 3 Results showed that PRADAXA 150mg reduced the risk of stroke and systemic embolism compared to warfarin across all three subgroups (permanent: PRADAXA 150mg: 1.11%/yr, warfarin: 1.58%/yr; paroxysmal: PRADAXA 150mg: 1.09%/yr, warfarin: 1.77%/yr; persistent: PRADAXA 150mg: 1.14%/yr, warfarin: 1.80%/yr; interaction p-value = 0.88). 3,6
About CHA 2DS 2-VASc
The CHA 2DS 2-VASc risk stratification scheme was developed by investigators at the University of Birmingham Centre for Cardiovascular Sciences in 2009, 4 and was included in the 2010 European Society of Cardiology Guidelines for the Management of Atrial Fibrillation. 7 The risk stratification scheme assigns one point for congestive heart failure/left ventrical dysfunction, hypertension, diabetes, vascular disease, age 65-74 and female sex, and assigns two points for age > 75 and previous stroke/TIA. 4 Patients with a CHA 2DS 2-VASc score of zero are considered to be at low risk of stroke, patients with a score of one are considered to be at moderate risk of stroke and patients with a score of two or higher are considered to be at high risk of stroke. 4
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